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7th European Congress of Chemotherapy and InfectionFlorence - Italy, October 19-22, 2005

GPs in France, clinical evaluation and prescriptions in respiratory tract infections

Pr Christian ChidiacService des Maladies Infectieuses et TropicalesINSERM 0230Hôpital de la Croix Rousse F69317 Lyonchristian.chidiac@chu-lyon.fr

Mars 2000 Les Outils de la Traçabilité 2

ABT prescriptions in France

Sources : EPPM - INSEE

100

120

140

160

180

200

220

1980

1982

1984

1986

1988

1990

1992

1994

1996

1998

2000

Antibiotic prescriptions GPs French population

3

ABT consumption EU - 2002Utilisationantibiotique en villeen Europe - 2002

0

5

10

15

20

25

30

35

FR GR LU PT IT BE SK HR PL IS IE ES FI BG CZ SI SE HU NO UK DK DE LV AT EE NL

DD

D p

er 1

000

inh

. p

er d

ay

OthersJ01B+J01G+J01X

Sulfonamides andtrimethoprim J01E

Quinolones J01M

Macrolides, Lincosam.,Streptogramins J01F

Tetracyclines J01A

CephalosporinsJ01D

Penicillins J01C

4

Germany Belgium Spain Italy France Netherland

Upper resp infections 36% 42% 41% 33% 56% 33%

Respiratory infections 32% 32% 21% 25% 28% 28%

Skin and soft tissu inf 3% 6% 15% 12% 5% 7%

UTI 17% 9% 13% 18% 7% 17%

Miscellaneous 12% 11% 10% 12% 4% 15%

Source : IMS

ABT Prescriptions in European coutries (2001)

5

Review of main guidelines in France

7

Common cold

Bacterial complication as acute otitis media, sinusitis

Risk factors for bacterial complication

Non-complicated common cold

Non-complicated common cold and risk factors

Common cold with bacterial complication

Inform parents/patients of clinical signs indicative of bacterial complication*

Symptomatic treatment

Symptomatic treatment and follow up

ABT treatment of the bacterial complication

In case of secondary bacterial complication

Investigate for

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Purulent AOM

OM with effusionRedness of tympanic membrane

No ABT No ABT

> 2 Years, mild symptoms

No ABT treatment

< 2 years,

> 2 years, marked symptoms

ABT treatment

Symptomatic treatment

Follow up 48-72 h

Amoxicillin clavulanic acid or cefuroxime-axetil or cefpodoxime-

proxetyl

Contra-indication for betalactam : erythromycin-sulfafurazole

pristinamycin

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Clinical signs of pharyngitis

Rapid Antigen TestPositive Negative

ABT*

Symptomatic treatment

*Amoxicillin,

Penicillin allergy : 2nd, 3rd G cephalosporin

Contra-indication for betalactams : pristinamycin (> 6 y), macrolide, telithromycin

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Clinical signs of pharyngitis

Rapid Antigen TestPositive Negative

ABT* Yes NoAcute rheumatic fever risk factors

Symptomatic treatmentCulturePositive Negative

*Amoxicillin,

Penicillin allergy : 2nd, 3rd G cephalosporin

Contra-indication for betalactams : pristinamycin (> 6 y), macrolide, telithromycin

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CAP : Healthy Adult

Pneumococcal or atypical ?

Pneumococcal

(acute onset)

Atypical (epidemic context, progressive

onset)

Oral amoxicillin 3g/d

Failure

Oral amoxicillin 3g/d

Or telithromycin,

or pristinamycin

Macrolide, Telithromycin, Pristinamycin,

Respiratory quinolone

Failure

Oral macrolide

Failure

Oral amoxicillin, Telithromycin, Pristinamycin,

Respiratory quinolone

Hospital if severity symptoms,

Complication, or failure of 2nd line ABT

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CAP : Adult with Risk Factors

Failure

Hospital

Parenteral 3rd G cephalosporin,

Amoxicillin clavulanic acid,

Respiratory quinolone

Severity symptoms Complication

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Classification of COPD

Stage I, II, III : FEV1/FVC < 70%,

Inconsistent chronic symptoms (cough, sputum production)

Dyspnea at restStage III : severe COPDFEV1 < 30% predictedor FEV1 < 50% + hypoxemia < 60 mmHg

Dyspnea of effortStage II : Moderate COPD

50% ≤ FEV1 < 80% predicted

No dyspnea of effortStage I : Mild COPD

FEV1 ≥ 80%

chronic symptoms : cough, sputum production

No dyspnea of effortStage 0 : FEV1/FVC > 70% predicted

Associated Clinical signsSeverity upon spirometry

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COPD : at risk patients*

One of the following characteristics

• FEV1 < 30% at baseline

• Hypoxemia at baseline (< 60 mmHg [8 Kpa])

• Frequent exacerbations (≥ 4/Year)

• Long term steroid treatment

• Comorbidity, underlying illness

• CAP history

* Risk of : – Severe respiratory failure, – Underlying illness decompensation, – GNB infection (H. influenzae excluded)

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Antibiotic management of AECOPD

One risk factor* at least

Yes

*Dyspnea (or FEV1 < 35%), hypoxemia, systemic steroid treatment, > 4 AECB / y, comorbidity, CAP history

Yes

Amoxicillin clavulanic acid, 2nd G oral cephalosporin (cefuroxim)

3rd G cephalosporin (cefpodoxime, cefotiam, ceftriaxone)

Respiratory quinolone

Failure :Sputum culture : Pseudomonas ?

X-ray

No

AmoxicillinMacrolide

PristinamycinTelithromycin

No

Follow upNo antibiotic

Clinical worseningor

Purulence of sputum

Acute Exacerbation of COPD stage I, II, III

Increased purulence of sputum + dyspnea and/or increased volume of sputum

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Controlling ABT prescriptions in France

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Controlling ABT prescriptions in France :History

• 1993 : « RMO » : French references • 1996 : Antibiotics and resistance in hospital (Andem)• 1998 : Observatory on use of ABT• 1999 : Fight against bacterial resistance (InVS)• 1999-02 : Official French Guidelines (Afssaps)• 2001 : National Antibiotic Plan (B Kouchner, Health Minister)• 2002 : Consensus conference : How to improve quality of

ABT prescriptions ? (French Society for Infectious Diseases)• 2002 : Ministerial circular : ABT referent doctors• 2002 : French social insurance campaign

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French 1993 references « RMO »

• « Experts » from the French Social Security

• Focus on useless or dangerous prescriptions

• “It is not indicated to prescribe….”

– Aminopenicillin and betalactamase inhibitor, 2nd or 3rd G

cephalosporin

– For no risk patients

– Suffering of seasonal respiratory infections, pharyngitis, or CAP

– Excluded : AOM, sinusitis, epiglottitis, bronchiolitis

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French 1993 references « RMO » : Results

Angine

Bronchite

IPPM/IMS France

Indication targeted by the « RMO » Indication not targeted by the « RMO »

0

10

20

30

40

50

60

70

80

P93 A93 P94 A94 P95 A95 P96 A96 P97 A97

Acute Otitis

Acute sinusitis

RMO + 12 months RMO + 4 yearsRMO

0

10

20

30

40

50

60

70

80

P93 A93 P94 A94 P95 A95 P96 A96 P97 A97

Pharyngitis

Bronchitis

% ABTRMO + 4 yearsRMO + 12 monthsRMO

% ABT

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Prescription : impact of RMO and Drug Promotion

0

5

10

15

20

25

30

35

40

85 87 89 91 93 95 97 99 '01

'03

Aminopenicillin

R.M.O

Amoxicillin price

0

5

10

15

20

25

30

35

40

85 87 89 91 93 95 97 99 '01

'03

Cephalosporins

R.M.O

0

5

10

15

20

25

30

35

40

85 87 89 91 93 95 97 99 '01

'03

Macrolides

R.M.O

Prescriptions Drug promotion Launching new drugSources : CAM, Dorema

Generic Drug

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Prescription : Impact of RMO andDrug Promotion

0

5

10

15

20

25

87 89 91 93 95 97 99 '01

'03

BL Inhibitors

R.M.O

0

5

10

15

20

25

87 89 91 93 95 97 99 '01

'03

C2G / C3G

R.M.O

0

5

10

15

20

25

87 89 91 93 95 97 99 '01

'03

Quinolones

R.M.O

Prescriptions Drug promotion Launching new drug

Sources : CAM, Dorema

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French National ABT Campaign

• General Public… – Television vidéo clips, radio, newspapers, magazines

• Medical Doctors…– Rapid Antigen Test for pharyngitis, formation– Therapeutic forms – Individual medical interview– Transmission of consumption information

• Childhood professionals, parents…– Information, education, meetings

• Patients…– Documentations, information ABT risks, resistance…

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ABT prescriptions since 1980 in France

Source : EPPM

100

110

120

130

140

150

160

170

180

190

200

210

220

1980 1981 1982 1983 1984 1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002

BASE 100 = 1980

(#)

(#)

(#)

(#)

(#)

(#)

(#)

(RMO)

(#)

(#) = Epidemy

(#)

(#)

Plan CNAMTS

(#)

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First Results : drop in prescriptions

Mean drop : -10,2 %

4,1 millions of prescriptions

-5,4 %1,9 millions ofprescriptions

En

mil

lio

ns

de

pre

sc

rip

tio

ns

D. Guillemot, CERBEP, Institut Pasteur - CNAMTS

34,7

40,7 M

38,8 M

36,6 M

30

32

34

36

38

40

42

2000-2001 2001-2002 2002-2003 2003-2004

33

ABT consumption by age

Since 2002,

23,1% < 15 years

20,6% 0- 5 years

D. Guillemot, CERBEP, Institut Pasteur - CNAMTS

0

0,5

1

1,5

2

2,5

3

1 2 3 4 5 6-10 11-15

16-20

21-25

26-30

31-35

36-40

41-45

46-50

51-55

56-60

61-65

66-70

71-75

76-80

81-85

86-90

90et +

Age (years)

Con

sum

ptio

n by

6 m

onth

s/in

habi

tant

winter 2001-2002 winter 2002-2003 winter 2003-2004

-0,5

-0,6

-0,3

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ABT prescriptions in respiratory infections1995-2004

Sinusite CIM 10

OtiteBronchite

Prescriptions/100 visits

Pharyngite

Source : EPPM

15

25

35

45

55

65

75

85

95

105

1995(été)

1996 1997 1998 1999 2000 2001 2002 2003 2004

Tonsillitis

Rhinopharyngitis

Bronchitis

Acute Otitis

Sinusitis CIM 9

Sinusitis CIM 10

Pharyngitis

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ABT treatment prescribed by GPs for CAP 2

No risk factors

Risk factors

total‡

In agreement with guidelines 22 (47%) 16 (34%) 38 (40)

Not in agreement with guidelines 25 (53%) 31 (66%) 56 (60%)

Total, N° 47 47 94

Pts without risk factor = amoxicillin or macrolide

Pts with risk factors = amoxicillin clavulanate, or oral cephalosporin ± macrolide or quinolone

Fantin B Chest 2001;120:185-192‡ p < 0.5

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Conclusion“Now, HERE, you see, it takes all the running

YOU can do, to keep in the same place”

Alice’s adventures trough the looking glass. L. Caroll